• Journal of Convergence for Information Technology
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• v.10 no.5
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• pp.134-142
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• 2020

This study aimed to determine whether there was a difference in lung functions of smokers according to the presence of carcinogenic genetic-metabolizing enzymes by comparing the results of lung functions and the presence of genetic metabolizing enzymes that metabolize tobacco substances. To achieve this, 31 smokers without no illness and no psychiatric history were selected (28 males and 3 females); they were aged 20 to 27 years and were physically and mentally healthy students attending K University. Their lung functions were measured, and gene polymorphisms of cytochrome P-450 1A1 (CYP1A1) related to metabolic activation of tobacco components and gene polymorphism of tumor protein 53 (TP53) related to lung cancer were analyzed. As a result, the mean values of lung function of TT and Arg / Arg without genetic mutations were the highest, and ANOVA analysis of CYP1A1 and lung functions showed that the P-value of FVC was 0.049, which was different between groups. In other words, there is no high mutation in Cytochrome P-450 1A1 (CYP1A1) gene, which is associated with the metabolic activation of tobacco components. In other words, In the absence of the mutant Cytochrome P-450 1A1 (CYP1A1) gene, which is associated with the metabolic activation of tobacco components, the value of FVC was high.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.1
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• pp.11-17
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• 2017

Purpose: Phenylketonuria (PKU) results from a deficiency of phenylalanine hydroxylase (PAH). The mutation of the PAH gene results in decreased phenylalanine hydroxylase enzyme activity in hyperphenylalaninemia (HPA) patients. This study reports ten cases of patients with the benign HPA genotype c.158G>A (p.Arg53His, R53H) variant in the PAH gene and aims to evaluate the clinical significance of the R53H variant. Methods: Ten Korean patients with the HPA genotype the R53H variant were included in this study. A retrospective medical record review was conducted. We characterized the phenotypes of the patients with HPA with the R53H variant using the following system: classic PKU, moderate PKU, mild PKU, Mild HPA, and benign HPA. Results: Five patients had the R53H variant with the "Pathogenic" variants (R413P, R241C, $Y356^*$, c.442-1G>A, $Y325^*$), Two patients had the "Likely pathogenic" variants ($W187^*$, A259T), Two patients had the "Uncertain significance" variants (R53H, G344D), and One patient had the "Not provided" variant (c.1066-14C>G). Nine patients genotyped with the R53H variant were the patient with benign HPA and One patient genotyped with the R53H homozygote was within normal range of plasma phenylalanine. None of the ten patients required dietary restriction of phenylalanine or pharmacotherapy to maintain their plasma phenylalanine levels and showed no clinical symptoms of HPA. Conclusion: Ten patients with HPA genotype the R53H variant were the patient with benign HPA and showed no clinical symptoms of HPA. Thus, the R53H variant, which was previously classified as an "Uncertain significance" mutation in HPA patients, should be re-classified as "Benign."

• Journal of Gastric Cancer
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• v.4 no.3
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• pp.169-175
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• 2004

Purpose: The tumor suppressor gene p53 has been shown to be a factor in the carcinogenesis or progression of gastric cancer. The mutant p53 has been reported to cause a higher risk of lymph-node metastasis. Futhermore, mutation of the p53 has been linked to a poor prognosis for gastric cancer. The heat shock protein-27 (HSP27), a stress protein, has also been reported to be a poor prognostic factor in ovarian and breast cancers. However, in gastric-cancer patients, controversies exist as to its influence on the prognosis. In the present study, we used an immunohistochemical stain to observe the effects of p53 and HSP27 on the clinicopathological factors and on the prognosis for gastric-cancer patients. Materials and Methods: To evaluate the significance of p53 and HSP27 in gastric cancer patients, we analyzed 212 cases of gastric cancer (stage I.IV). Tissue samples of 212 patients were stained immunohistochemically for the mutant p53 protein and for HSP27. The correlations between protein expression and the clinicopathological factors were investigated. Results: The overall expression rates for p53 and HSP27 were $36.9\%\;and\;27.8\%$, respectively. p53 and HSP27 were correlated to each other because the HSP27 expression rate was higher in the p53-positive group (P=0.046). Statistically, the p53 and the HSP27 expression rates were significantly increased in the case of tumor invasiveness, lymphatic metastasis and vessel involvement. Therefore, they play a role in cancer progression. The 5-year survival rates of the p53-positive and the p53-negative groups were $62.8\%\;and\;60.1\%$, respectively (P=0.793) while the 5-year survival rates for the HSP27-positive and HSP27-negative groups were $54.2\%\;and\;63.1\%$, respectively (P=0.090). Conclusion: p53 and HSP27 were correlated to each other in our immunohistochemical study of gastric carcinomas and they were not independent prognostic factors in gastric- cancer patients. However, further studies are needed to determine their prognostic values for gastric-cancer patients.

• Journal of Genetic Medicine
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• v.8 no.1
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• pp.53-57
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• 2011

Purpose: Wilson disease is an autosomal recessive disorder which causes excessive copper accumulation in the hepatic region. So far, ATP7B gene is the only disease-causing gene of Wilson disease known to date. However, ATP7B mutations have not been found in ~15% of the patients. This study was performed to identify any causative gene in Wilson disease patients without an ATP7B mutation in either allele. Materials and Methods: The sequence of the coding regions and exon-intron boundaries of the five ATP7B-interacting genes, ATOX1, COMMD1, GLRX, DCTN4, and ZBTB16, were analyzed in the 12 patients with Wilson disease. Results: Three nonsynonymous variants including c.1084A>G (p.Thr362Ala) in the exon 12 of the DCTN4 gene were identified in the patients examined. Among these, only p.Thr362Ala was predicted as possibly damaging protein function by in silico analysis. Examination of allele frequency of c.1084A>G (p.Thr362Ala) variant in the 176 patients with Wilson disease and in the 414 normal subjects revealed that the variant was more prevalent in the Wilson disease patients (odds ratio [OR]=3.14, 95% confidence interval=1.36-7.22, P=0.0094). Conclusion: Our result suggests that c.1084A>G (p.Thr362Ala) in the ATP7B-interacting DCTN4 gene may be associated with the pathogenesis of Wilson disease.

• Korean Journal of Clinical Laboratory Science
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• v.40 no.2
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• pp.98-105
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• 2008

Colorectal carcinoma from various cancers is fourth ranked occurred to Korean. Due to western dietary life, this cancer has been increased continuously. Therefore, the further study will be needed to find a candidate gene involved in the development and progression of colorectal carcinoma as well as to diagnose and treatment helpfully. The purpose of this study was designed to find a carcinogenesis gene using microsatellite marker on chromosomes 7th and 20th from 30 colon cancer patients. The amplification was investigated in order of D20S97 57% (17/30), D20S101 57% (17/30), D20S119 53% (16/30), D7S483 50% (15/30), D7S495 47% (14/30), D7S498 47% (14/30). The genetic mutation pattern depends on loci of colorectal carcinoma was shown highly amplified with 3.77 from colon cancer than with 2.08 from right colorectal carcinoma (P<0.018). The genetic mutation with lymph nodes was investigated higher with 4.13 at metastasized group than with 1.93 at non-metastasized group (P<0.001). There was no difference at comparison between histological classfication and serological CEA increase as well as on genetic mutated pattern depends on disease stage. It is suggested that the amplification on chromosomes 7q and 20q determines a pivotal role from first stage to metastasis cancer and also functions as an useful marker on diagnosis and treatment of colorectal carcinoma patients as well as follow-up checkup. Recently, the diagnosis and study using genetic analyzer are necessary for efficient application. Fortunately, several university hospitals run this genetic analyzer currently so it is expected that this method makes full use of clinical application.

• Korean Journal of Head & Neck Oncology
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• v.22 no.1
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• pp.8-14
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• 2006

Objectives: The p53 tumor suppressor gene has a key role in cellular control mechanisms involving apoptosis and DNA repair, leading to the G1 arrest following DNA damage. Its mutation is one of the most frequent alterations in human cancers. Ki-67 is identified in replicating cells of both benign and malignant lesions, so it can be the predictor of proliferative activity. The aim of this study is to evaluate the expression of p53 and Ki-67 in salivary gland tumors. Materials and Methods: Immunohistochemical analysis was used to detect expression of p53 and Ki-67 in paraffin-embedded samples from 31 benign and 27 malignant salivary gland tumors. Results were analyzed between benign and malignant tumors and compared with the clinical parameters such as stage and recurrence in malignant tumors. Results: p53 overexpression was detected in 19.6% of benign tumors and 40.7% of malignant tumors, but there was no statistical significance. p53 was significantly expressed in Warthin's tumor(45.5%) compared with pleomorphic adenoma(5.9%). Only 5.9% of pleomorphic adenoma were positive for p53, while 60% of carcinoma ex pleomorphic adenoma were positive for p53. Ki-67 was expressed in 3.2% of benign tumors and 51.9% of malignant tumors, which showed significant higher expression in malignant tumors. In malignant tumors, p53 and Ki-67 expressions bore no correlation to stage and recurrence. Conclusion: p53 overexpression is not associated with the progression of malignant tumors, and Ki-67 overexpression can be used as biologic indicator of malignant salivary gland tumors.

• Molecules and Cells
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• v.20 no.2
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• pp.228-234
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• 2005

Caenorhabditis elegans him-6 mutants, which show a high incidence of males and partial embryonic lethality, are defective in the orthologue of human Bloom's syndrome protein (BLM). When strain him-6(e1104) containing a missense him-6 mutation was irradiated with ${\gamma}$-rays during germ cell development or embryogenesis, embryonic lethality was higher than in the wild type, suggesting a critical function of the wild type gene in mitotic and pachytene stage germ cells as well as in early embryos. Even in the absence of ${\gamma}$-irradiation, apoptosis was elevated in the germ cells of the him-6 strain and this increase was dependent on a functional p53 homologue (CEP-1), suggesting that spontaneous DNA damage accumulates due to him-6 deficiency. However, induction of germline apoptosis by ionizing radiation was not significantly affected by the deficiency, indicating that HIM-6 has no role in the induction of apoptosis by exogenous DNA damage. We conclude that the C. elegans BLM orthologue is involved in DNA repair in promeiotic cells undergoing homologous recombination, as well as in actively dividing germline and somatic cells.

• Tuberculosis and Respiratory Diseases
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• v.65 no.6
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• pp.476-486
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• 2008

Background: TRAIL (TNF-related apoptosis inducing ligand) is a newly identified member of the TNF gene family which appears to have tumor-selective cytotoxicity due to the distinct decoy receptor system. TRAIL has direct access to caspase machinery and induces apoptosis regardless of p53 phenotype. Therefore, TRAIL has a therapeutic potential in lung cancer which frequently harbors p53 mutation in more than 50% of cases. However, it was shown that TRAIL also could activates $NF-{\kappa}B$ in some cell lines which might inhibit TRAIL-induced apoptosis. This study was designed to investigate whether TRAIL can activate $NF-{\kappa}B$ in lung cancer cell lines relatively resistant to TRAIL-induced apoptosis and inhibition of $NF-{\kappa}B$ activation using proteasome inhibitor MG132 which blocks $I{\kappa}B{\alpha}$ degradation can sensitize lung cancer cells to TRAIL-induced apoptosis. Methods: A549 (wt p53) and NCI-H1299 (null p53) lung cancer cells were used and cell viability test was done by MTT assay. Apoptosis was confirmed with Annexin V assay followed by FACS analysis. To study $NF-{\kappa}B$-dependent transcriptional activation, a luciferase reporter gene assay was used after making A549 and NCI-H1299 cells stably transfected with IgG ${\kappa}-NF-{\kappa}B$ luciferase construct. To investigate DNA binding of $NF-{\kappa}B$ activated by TRAIL, electromobility shift assay was used and supershift assay was done using anti-p65 antibody. Western blot was done for the study of $I{\kappa}B{\alpha}$ degradation. Results: A549 and NCI-H1299 cells were relatively resistant to TRAIL-induced apoptosis showing only 20~30% cell death even at the concentration 100 ng/ml, but MG132 ($3{\mu}M$) pre-treatment 1 hour prior to TRAIL addition greatly increased cell death more than 80%. Luciferase assay showed TRAIL-induced $NF-{\kappa}B$ transcriptional activity in both cell lines. Electromobility shift assay demonstrated DNA binding complex of $NF-{\kappa}B$ activated by TRAIL and supershift with p65 antibody. $I{\kappa}B{\alpha}$ degradation was proven by western blot. MG132 completely blocked both TRAIL-induced $NF-{\kappa}B$ dependent luciferase activity and DNA binding of $NF-{\kappa}B$. Conclusion: This results suggest that inhibition of $NF-{\kappa}B$ can be a potentially useful strategy to enhance TRAIL-induced tumor cell killing in lung cancer.

• Journal of Nutrition and Health
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• v.35 no.8
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• pp.870-879
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• 2002

The purpose of this study was to investigate the obesity and state of dietary intake of 216 young Korean females, and the influence of $\beta$-II, III Adrenergic receptor (AR) gene polymorphism upon obesity and dietary intake. The average weight, height and BMI of the subjects were 160 cm, 54 kg, and 20.9 kg/$m^2$, respectively. The average triceps skinfold thickness, waist circumference, hip circumference and WHR were 21.7mm, 73.1cm, 93.3cm and 0.78, respectively. The results of body composition measurement using bioimpedance method, average body fluid, body protein, mineral mass and body fat were 29.271, 7.22 kg, 6.79 kg and 19.16 kg, respectively. A dietary survey was conducted using 24-hour recall method. Average calorie intake was 1621 ㎉, which is 81% of Korean RDA. We detected 182 (84.3%) Gln27 (QQ) homozygotes and 34 (15.7%) Gln27Glu (QE) heterozygotes for $\beta$-II AR polymorphism. For $\beta$-III AR polymorphism, we detected 163 (75.5%) Trp64 (WW) and 53 (24.5%) Trp 64Arg (WR). The results of comparing of obesity by $\beta$-II AR gene polymorphism, obesity index and BMI of QE type were slightly higher than those of the QQ type. For $\beta$-III AR gene polymorphism, the mean BMI, obesity index, fat mass and percent body fat (%) of the WR type were significantly higher than those of the WW type (p < 0.05). These findings suggest that genetic variability in the human $\beta$-III AR is associated with obesity among young Korean females. We also evaluated the effect of the simultaneous presence of the $\beta$-II AR and $\beta$-III AR polymorphism on obesity. We found that the BMI and obesity index of the mutant type in both $\beta$-II AR and $\beta$-III AR were significantly higher than those of the type that has only one gene mutation or has no mutation (p < 0.05), indicating a synergistic effect of $\beta$-II AR and $\beta$-III AR polymorphism on obesity. No association was found between $\beta$-II Ad or $\beta$-III AR polymorphism and dietary intake.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.1
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• pp.49-53
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• 2012

X-linked adrenoleukodystrophy (ALD) is a rare inherited metabolic disease which results in impaired peroxisomal ${\beta}$-oxidation and the accumulation of very long chain fatty acids (VLCFA) in the adrenal cortex, the myelin of the central nervous system, and the testes. X-linked ALD is caused by mutations in the ABCD1 gene encoding an ATP-binding cassette transporter superfamily located in the peroxisomal membrane. This disease is characterized by a variety of phenotypes. The classic childhood cerebral ALD is a rapidly progressive demyelinating condition affecting the cerebral white matter before the age of 10 years in boys. We report the case of a 8-year-old with childhood cerebral X-linked ALD who developed inattention, hyperactivity, motor incoordination and hemiparesis. We diagnosed ALD with elevated plasma very long chain fatty acid level and diffuse high signal intensity lesions in both parieto-occipital white matter and cerebellar white matter in brain MRI. We identified a novel c.983delT (p.Met329CysfsX7) mutation of the ABCD1 gene. There is no correlation between X-ALD phenotype and mutations in the ABCD1 gene. Further studies for searching additional non-genetic factor which determine the phenotypic variation will be needed.